Objective To design and synthesize derivatives of oleanolic acid and ursolic acid, and investigate their anti-hepatitis C virus （HCV） activity along with that of common triterpenoid acids. To explore the structure-activity relationship and provide a reference for the research of anti-HCV drugs derived from natural products through obtaining compounds with higher activity. Methods Oleanolic acid and ursolic acid were directly reacted with corresponding amines using PyBOP as a condensing agent in the presence of DIEA. Alternatively, the target compounds were prepared through PCC oxidation followed by the Baeyer-Villiger reaction catalyzed by m-CPBA. In vitro anti-HCV activity was tested using the HCVcc infection model. Molecular docking was performed by Autodock software to investigate the interaction between the active compounds and HCV NS5B. Results Oleanolic acid, glycyrrhetinic acid, ursolic acid, and asiatic acid all exhibited certain anti-HCV effects. Specifically, oleanolic acid derivatives OA2-OA4, OA6, and OA7, as well as ursolic acid derivatives UA1 and UA2, demonstrated superior anti-HCV activity compared to their parent compounds. Preliminary structure-activity relationship analysis revealed that introducing a bulky group to 28-COOH of oleanolic acid and ursolic acid enhanced their activity. Molecular docking results demonstrated that the active compounds could stably bind to HCV NS5B, thereby exhibiting antiviral activity. Conclusion Pentacyclic triterpenoids possessed anti-HCV effects, and their derivatives coud be synthesized to obtain more active compounds. The anti-HCV mechanism of these compounds may be associated with their inhibition of NS5B.

Objective To investigate the relationship between interleukin-1β (IL-1β) and miR-185-5p in the process of joint injury in acute gouty arthritis (AGA). Methods The serum miR-185-5p levels of 89 AGA patients and 91 healthy volunteers were detected by real-time quantitative PCR. The correlation between miR-185-5p expression level and VAS score or IL-1β expression level was evaluated by Pearson correlation coefficient method. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of miR-185-5p in AGA. THP-1 cells were induced by sodium urate (MSU) to construct an in vitro acute gouty inflammatory cell model. After the expression level of miR-185-5p in THP-1 cells was upregulated or downregulated by transfection of miR-185-5p mimics or inhibitors in vitro, inflammatory cytokines of THP-1 cells, such as IL-1β, IL-8 and tumor necrosis factor α (TNF-α), were detected by ELISA. The luciferase reporter gene assay was used to determine the interaction between miR-185-5p and the 3'-UTR of IL-1β. Results Compared with the healthy control group, the expression level of serum miR-185-5p in AGA patients was significantly reduced. The level of serum miR-185-5p was negatively correlated with VAS score and IL-1β expression level. The area under the curve (AUC) was 0.905, the sensitivity was 80.17% and the specificity was 83.52%. Down-regulation of miR-185-5p significantly promoted the expression of IL-1β, IL-8 and tumor necrosis factor (TNF-α), while overexpression of miR-185-5p showed the opposite results. Luciferase reporter gene assay showed that IL-1β was the target gene of miR-185-5p, and miR-185-5p negatively regulated the expression of IL-1β. Conclusion miR-185-5p alleviates the inflammatory response in AGA by inhibiting IL-1β.
Humans ; 3' Untranslated Regions ; Arthritis, Gouty/genetics* ; Interleukin-1beta/genetics* ; Interleukin-8 ; Luciferases ; MicroRNAs/genetics* ; Tumor Necrosis Factor-alpha

ObjectiveTo improve the response capabilities to disasters and prevent major epidemics， it is of practical use to study the capability evaluation system of the national emergency medical rescue team that combines theoretical training and practical exercises， to enhance the overall quality of the teams. MethodsFirst， a capability assessment system for the national emergency medical rescue team was constructed based on the INSARAG External Classification （IEC） standards of the national emergency medical rescue team. Then， based on the outcome based education （OBE） concept， we conducted innovative research on the curriculum design and exercise programs for team building and member training. Finally， an empirical analysis was conducted on the effectiveness of the evaluation system and training exercises based on the statistical analysis of the comprehensive quality evaluation of the Shanghai national emergency medical rescue team from 2020 to 2023， as well as the empirical analysis of the rescue exercise on the Cruise of spectrum. ResultsBased on the linear regression analysis of each core competency indicators， the five core competencies in the evaluation system， including rescue skills， medical and health knowledge， disaster coping ability， team cooperation ability， and mental resilience training， were positively correlated with the cumulative number of trainings （r=0.71， r=0.76， r=0.81， r=0.84， r=0.96，all P<0.05）， indicating that the training was effective and the course design was reasonable. Empirical cases showed that the three-dimensional rescue drill model had remarkable results in the actual combat application and ability improvement of team members. ConclusionThe training courses and drills designed based on the three-level assessment system are effective in improving the comprehensive capabilities of the national emergency medical rescue team.

Objective To explore the imaging features, clinical outcome, and prognosis of indeterminate pulmonary nodules (IPN) in patients with high-grade soft tissue sarcoma. Methods A retrospective study of 82 patients with high-grade soft tissue sarcoma who have IPNs. The clinical characteristics, imaging features of IPN, and survival of patients were analyzed with statistical software. Results The IPN size of 82 patients was 6.453±0.864 mm. IPN diameter, shape, density, and nodule discovery interval may be CT imaging features related to malignancy tendency. Age (HR=1.047, 95%CI: 1.007-1.088) and interval between each nodule discovery (HR=3.194, 95%CI: 1.052-9.694) are independent factors that affect the survival of patients with malignant IPN. Conclusion The imaging features of chest CT may provide important guidance for determining the nature and survival prognosis of benign and malignant nodules.

【Objective】 To investigate the efficacy and surgical technique of total laparoscopic radical cystectomy with intracorporeal ileal conduit urinary diversion, so as to provide reference for the selection of surgery for patients with bladder cancer. 【Methods】 Clinical data of 48 patients with bladder cancer who underwent laparoscopic radical cystectomy during Mar.2017 and Aug.2022 in our hospital were retrospectively analyzed, including 23 cases who received traditional laparoscopic radical cystectomy combined with extracorporeal ileal conduit, and 25 who received total laparoscopic radical cystectomy with intracorporeal ileal conduit.The operation time, blood loss, postoperative intestinal function recovery time, drainage tube removal time and hospital stay were compared between the two groups. 【Results】 All procedures were successfully performed, and no Clavien-Dindo>grade 3 complications were observed.The operation time, and amount of estimated blood loss of the traditional group and total laparoscopic radical group were (227.0±46.4) min vs. (253.6±58.9) min, and (131.7±79.8) mL vs. (154.0±93.0) mL, respectively.There were no differences in postoperative intestinal function recovery time and drainage tube removal time (P>0.05).The hospital stay was shorter in the total laparoscopic radical group than in the traditional group (P=0.035). 【Conclusion】 Total laparoscopic radical cystectomy with intracorporeal ileal conduit urinary diversion is safe and feasible.which is comparable to the traditional laparoscopic surgery, while the hospital stay in the total laparoscopic group is shorter, which is conducive to rapid postoperative recovery.

Mitral valve replacement is one of the most common heart valve surgeries in China. In recent years, with the increase in degenerative valve diseases, older patients, and the progress of anti-calcification technology of biological valves, the proportion of mitral valve biological valve replacement has been increasing year by year. After the damage of traditional mitral valve biological valves, re-operation of valve replacement with thoracotomy is required. However, the adhesion between the heart and sternum, as well as the damage caused by cardiopulmonary bypass and cardiac arrest, can cause significant trauma to elderly patients and those with multiple organ dysfunction, leading to increased mortality and complication rates. In recent years, interventional valve surgery, especially transcatheter valve-in-valve surgery, has developed rapidly. This procedure can correct the damaged mitral valve function without stopping the heart, but there are still many differences between its technical process and conventional aortic valve replacement surgery. Therefore, organizing and writing multicenter expert recommendations on the technical process of transcatheter valve-in-valve surgery for damaged mitral valve biological valves is of great significance for the training and promotion of this technology.

Objective: To explore the causal relationship between the abundance of intestinal flora(IF) and the risk of developing acute myeloid leukemia(AML) using two-sample bidirectional Mendelian randomization(MR) methods. Methods: The MiBioGen Consortium and FinnGen databases were utilized for the IF abundance and AML genome-wide association datasets, respectively. The primary analysis method entailed variance inverse weighting, supplemented by weighted median test, while heterogeneity was assessed using Cochran′sQtest. Additionally, MR-PRESSO was employed to identify any outliers, while MR-Egger intercept was utilized to evaluate horizontal pleotropy. Results: Higher abundance of genetically determinedDialister(P=0.034,OR=4.373,95%CI:1.329-14.392),Veillonaceae(P=0.009,OR=2.029,95%CI:1.839-3.866), andLachnospiraceae UCG008(P=0.034,OR=3.827,95%CI:1.107-13.228) were found to be linked to an increased risk of AML. In contrast,Ruminococcaceae(P=0.042,OR=0.176, 95%CI:0.033-0.939) andPeptococcaceae(P=0.025,OR=0.168, 95%CI:0.035-0.803) were associated with a reduced risk of this disease. Conclusion Higher levels of theDialister, theVeillonellaceae, and theLachnospiraceae UCG008are risk factors for AML, while the familiesRuminococcaceaeandPeptococcaceaeare identified as protective factors against AML.

Objective By using the computational fluid mechanic(CFD)method the tandem carotid artery stenosis(TCAS)was simulated on the model,and to compare the postoperative hemodynamic changes of different surgical procedures.Methods One patient with tandem stenosis of internal carotid artery(ICA)and common carotid artery(CCA)was selected.CFD technique was used to establish four three-dimensional(3-D)models of the carotid bifurcations,including one model of a real patient and three models of presumptive surgery.The hemodynamic analysis was performed with these models so as to explore the development mechanism of TCAS and to discuss the selection of suitable surgical plan.Results In tandem stenosis,the stenosis was preferentially formed in CCA and subsequently led to ICA stenosis.The local hemodynamic situation in TCAS was more complex and more risky than in single carotid artery stenosis.In tandem stenosis,the treatment of one stenosis site would affect the blood flow at the next stenosis site and cause restenosis or plaque rupture.Conclusion In treating patients with TCAS,CFD simulation examination should be performed when the surgical plan is formulated,which can help clinicians to predict the postoperative changes in blood flow and to choose the appropriate surgical plan.